The effects of arachidonic and other fatty acids on canine neutrophil metabolism.
The effect of arachidonic acid on the metabolic activity and chemiluminescence of canine neutrophils was investigated to gain further insight into its role in the neutrophil metabolic burst. Arachidonic acid was found to stimulate metabolic activity and luminol-augmented chemiluminescence. The increased metabolic activity was detected by both oxygen uptake measurements and assays of hexose monophosphate shunt activity. An inhibitor of lipoxygenase and cyclooxygenase, 5, 8, 11, 14-eicosatetraynoic acid prevented the hexose monophosphate shunt response to arachidonic acid. Aspirin or indomethacin, blockers of cyclooxygenase, inhibited chemiluminescence but failed to block the metabolic response to arachidonic acid. Since superoxide dismutase and 2-deoxyglucose, a blocker of glucose metabolism, inhibited the chemiluminescent response of neutrophils to arachidonic acid, it is likely that oxygen radicals produced via the hexose monophosphate shunt are required for the chemiluminescent reaction. In addition it was found that inhibition of cyclooxygenase activity blocked chemiluminescence but not the metabolic stimulation induced by sodium fluoride, suggesting that the chemiluminescence stimulated by sodium fluoride is associated with endogenous fatty acid stores. From these studies it can be concluded that arachidonic acid products of the cyclooxygenase pathway do not play a significant role in the metabolic response of neutrophils when arachidonic acid or sodium fluoride is the stimulant while the lipoxygenase pathway appears to be involved. The metabolic response is not linked to the chemical reaction that caused neutrophil chemiluminescence, although the chemiluminescent response depends on hexose monophosphate shunt activity and presumably the oxygen radicals that ultimately result from that process.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D004285:Dogs; D005459:Fluorides / Q000494:pharmacology; D066298:In Vitro Techniques; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D008163:Luminescent Measurements; D008274:Magnesium / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects
D001095:Arachidonic Acids; D001786:Blood Glucose; D008041:Linoleic Acids; D009829:Oleic Acids; D016718:Arachidonic Acid; D019301:Oleic Acid; D019787:Linoleic Acid; D008274:Magnesium; D005459:Fluorides; D002118:Calcium